Testicular Cancer

Aka: Testicular Cancer, Testicular Neoplasm, Testicular Tumor

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II. Epidemiology

  1. Accounts for 1% of all cancers in males
  2. Age of onset
    1. Peak age: 30-34 years old (ranges 12 to 35)
    2. Most common cancers in males ages 15 to 34 years
    3. Rare in early childhood
  3. Incidence: Has doubled since 1960s
    1. New cases in U.S. (2018): 8850 (410 deaths)
    2. Cases per 100,000: 5.6 (14.6 at age 30-34 years old)
    3. Geographic variation
      1. Highest rates: Scandanavia and Germany, hispanic, native alaskan and native american
      2. Lowest rates: Asia and Africa

III. Risk Factors

  1. Cryptorchidism (Undescended Testicle)
    1. Accounts for 10% of cases
    2. Confers 2.9 to 6.3 fold increased risk
    3. Risk increases
      1. Intraabdominal Testicle (contrast with inguinal)
      2. Bilateral crytorchidism
      3. Repair after age 12 years old (5 fold increased risk)
      4. Even with early orchiopexy, Testicular Cancer Relative Risk is still 2.2
  2. Caucasian (4-5 fold increased risk)
  3. Testicular Cancer in the contralateral Testicle (Relative Risk 12)
  4. Family History of Testicular Cancer
    1. Father with Testicular Cancer increases Relative Risk 3.8 fold
    2. Brother with Testicular Cancer increases risk 6-10 fold
  5. Testicular Germ Cell Tumor 1 (Chromosome Xq27)
  6. Tobacco Abuse
    1. Ongoing Tobacco use with a >12 pack year history confers 2 fold risk
  7. Infertility (Relative Risk 1.6 to 2.8)
  8. Testicular atrophy
  9. Testicular dysgnesis
  10. HIV Infection

IV. Pathophysiology

  1. Germinal or Germ Cell Tumors (95-97%)
    1. Seminoma (most common, 50% of germ cell tumors)
    2. Non-Seminoma Germ Cell tumors (NSGCT)
      1. Embryonal cell carcinoma
      2. Yolk Sac tumor (postpubertal)
      3. Teratoma (postpubertal)
      4. Trophoblastic Tumor (e.g. Choriocarcinoma)
  2. Nongerminal tumors (sex cord-stromal tumors)
    1. Leydig cell tumor (associated with Precocious Puberty)
    2. Sertoli cell tumor
    3. Granulosa Cell Tumor
  3. Mixed germ cell and stromal tumors
    1. Gonadoblastoma
  4. Miscellaneous tumors
    1. Hemangioma
    2. Hematolymphoid tumors
    3. Adenocarcinoma of the collecting duct or rete Testis

V. Symptoms

  1. Painless, firm Testicular Mass found incidentally
  2. Dull ache in Scrotum
  3. Scrotal heaviness
  4. Vague Abdominal Pain

VI. Symptoms: Red Flag Presentations

  1. Minor Scrotal Trauma causes significant injury (Scrotal Hematoma, Hydrocele)
  2. Epididymitis with swelling or tenderness that fails to improve with Antibiotic therapy

VII. Signs

  1. Painless asymmetric, hard, firm Testicular Mass
  2. Transilluminate for reactive Hydrocele
  3. Evaluate for Inguinal Lymphadenopathy (as well as Supraclavicular Lymphadenopathy)
    1. Lymphoma
    2. Leukemia
    3. Metastatic Disease
  4. Evaluate for Gynecomastia (as well as Precocious Puberty signs)
    1. Overall 10% of patients (30% of Leydig cell tumors) produce bHCG
  5. Evaluate for systemic disease (metastases present in 5% of patients)
    1. Hemoptysis, cough or Dyspnea from pulmonary metastases
    2. Supraclavicular mass from Lymph Node metastases
    3. Abdominal mass from retroperitoneal spread
    4. Lumbar back pain from Vertebral metastases

VIII. Differential Diagnosis

  1. See Testicular Mass

IX. Staging

  1. Based on TNMS classification
    1. T: Tis (carcinoma in situ) to T4 (tumor invades Scrotum)
      1. T1: Tumor limited to Testis (T1a < 3cm in size)
      2. T2: Lymphovascular invasion or other spread short of spermatic cord
      3. T3: Spermatic cord involvement
      4. T4: Scrotal involvement
    2. N: N0 (no Lymph Nodes involved) to N3 (one Lymph Node and 5 cm mass)
      1. N1: One or more Lymph Node masses <2 cm
      2. N2: One or more Lymph Node masses 2-5 cm
      3. N3: Lymph Node masses >5 cm
    3. M: M0 (no distant metastases) to M1 (distant metastases present)
      1. M1a: Nonretroperitoneal nodal or pulmonary metastases
      2. M1b: Nonpulmonary visceral metastases
    4. S: S0 (normal Tumor Markers) to S3 (Tumor Markers significantly increased)
  2. Staging Summary (* denotes ANY)
    1. Note: Each stage is subdivided (Ia-b, IIa-c, IIIa-c )
    2. Stage I: Testicular Cancer involving Testicle only (T* N0 M0 S0)
      1. LDH <1.5x normal, bHCG <5k mIU/ml, AFP <1k ng/ml
    3. Stage II: Metastases to retroperitoneal nodes (T* N* M0 S0-1)
      1. LDH 1.5-10x normal, bHCG 5-50k mIU/ml, AFP <1-10k ng/ml
    4. Stage III: Metastases above diaphragm or to viscera (T* N* M1 S*)
      1. LDH >10x normal, bHCG >50k mIU/ml, AFP >10k ng/ml

X. Imaging

  1. Scrotal and Testicular Ultrasound
    1. Differentiate intratesticular mass (presumed cancer) from extratesticular mass
    2. Efficacy in Testicular Cancer
      1. Test Sensitivity: 92-98%
      2. Test Specificity: 95-99.8%
  2. Additional studies for cancer staging and evaluation for metastases
    1. CT Abdomen and Pelvis
    2. Chest XRay or CT Chest

XI. Labs: Tumor Markers

  1. Alpha fetoprotein (aFP)
    1. Secreted by non-seminoma GCT or mixed tumors
    2. Not secreted by a pure seminoma or Choriocarcinoma
    3. Falls to <25 ng/ml by 25-35 days after orchiectomy
  2. Human Chorionic Gonadotropin (bHCG)
    1. Secreted by 50% non-seminoma GCT or mixed tumors
    2. Secreted by 10% of seminomas
    3. Undetectable by 5 to 8 days after orchiectomy
  3. Lactate Dehydrogenase (LDH, especially LDH-1)
    1. Elevated in 60% of patients with non-seminoma GCT
    2. Increases with tumor burden (esp. widespread and metastatic cancer)
  4. Other lab testing
    1. Comprehensive metabolic panel

XII. Management: Treatments

  1. Surgery: Radical orchiectomy by inguinal approach
    1. High ligation spermatic cord (to Internal Inguinal Ring)
    2. Further therapy directed by histology
  2. Chemotherapy
    1. Agents (typically Cisplatin combined with one or both of the other agents)
      1. Carboplatin
      2. Cisplatin (Platinol)
      3. Etoposide (Vepesid)
      4. Bleomycin (Blenoxane)
    2. Indications
      1. Advanced spread of disease
      2. Advanced stage seminoma and non-seminomas
  3. Radiotherapy
    1. Indicated for early-stage seminomas

XIII. Management: Seminoma

  1. Radical orchiectomy is performed for all stages
  2. Stage I (T1-T3 tumors)
    1. Active surveillance (preferred) OR
    2. Single-agent Carboplatin or Radiotherapy
  3. Stage II
    1. Stage IIA
      1. Radiotherapy (preferred) OR
      2. Etoposide-Cisplatin for 4 cycles OR
      3. Bleomycin-Etoposide-Cisplatin for 3 cycles
    2. Stage IIB
      1. Etoposide-Cisplatin for 4 cycles (preferred) OR
      2. Bleomycin-Etoposide-Cisplatin for 3 cycles (preferred) OR
      3. Radiotherapy of regional Lymph Nodes
    3. Stage IIC
      1. Etoposide-Cisplatin for 4 cycles OR
      2. Bleomycin-Etoposide-Cisplatin for 3 cycles
  4. Stage III
    1. Etoposide-Cisplatin for 4 cycles OR
    2. Bleomycin-Etoposide-Cisplatin for 3 cycles

XIV. Management: Nonseminoma

  1. Radical orchiectomy is performed for all stages
  2. Stage I (IA and IB)
    1. Active surveillance (preferred for IA) OR
    2. Retroperitoneal Lymph Node dissection (RPLND) OR
    3. Bleomycin-Etoposide-Cisplatin for 1-2 cycles (if Stage IB)
  3. Stage II (IIA to IIC)
    1. Etoposide-Cisplatin for 4 cycles OR
    2. Bleomycin-Etoposide-Cisplatin for 3 cycles OR
    3. Radiotherapy (for Stage IIA and select Stage IIB cases)
  4. Stage III
    1. Stage IIIA
      1. Etoposide-Cisplatin for 4 cycles OR
      2. Bleomycin-Etoposide-Cisplatin for 3 cycles OR
    2. Stage IIIB
      1. Bleomycin-Etoposide-Cisplatin for 4 cycles
    3. Stage IIIC
      1. Bleomycin-Etoposide-Cisplatin for 4 cycles OR
      2. Etoposide-Ifosfamide-Cisplatin for 4 cycles (in select cases)

XV. Monitoring: Five year

  1. Surveillance after initial management is typically for 5 years
    1. Exact monitoring protocols vary by tumor type and stage
    2. This section summarizes more specific guidelines
  2. History and physical
    1. Initially every 2-3 months, then every 3-6 months and then annually
  3. Abdominal and Pelvic CT
    1. Initially every 3-6 months, then every 6-12 months
    2. PET/CT surveillance may be obtained in higher stage cancers
  4. Chest XRay
    1. As indicated in Stage I Seminoma, and in other tumors every 2-6 months initially, then every 6-12 months
    2. CT Chest may be indicated in symptomatic patients
  5. Tumor Markers (Serum bHCG, AFP levels, Lactate Dehydrogenase)
    1. Obtained at each history and physical
    2. Optional in Stage I and IIA Seminoma
    3. False Negatives in up to 35% of non-seminoma recurrence

XVI. Prevention

  1. Testicular Cancer screening is not recommended in asymptomatic men (USPTF, NCI, AAFP)
  2. Testicular Self-Exam

XVII. Prognosis

  1. Overall 5 year survival > 95% (Previously 63% in 1963)
    1. Stage I Five year survival: 98%
    2. Stage II Five year survival: 97%
    3. Stage III Five year survival: 72%
  2. Cure rate is 99% for early Testicular Cancer without metastases
  3. When relapse occurs, it is typically within 18 months of Chemotherapy
  4. Risk of cancer in opposite Testicle: 2 to 5%

XVIII. Complications

  1. Testicular Cancer related
    1. Infertility
  2. Radiation-related
    1. Cardiac toxicity
    2. Leukemia or other secondary malignancy
  3. Chemotherapy-related
    1. General: Azoospermia, Leukemia or other secondary malignancy
      1. Cardiovascular mortality increases 5-fold in the first year after Chemotherapy
        1. Fung (2015) J Clin Oncol 33(28): 3105-15 [PubMed]
    2. Bleomycin: Lung toxicity
    3. Etoposide: Neurotoxicity with secondary Peripheral Neuropathy
    4. Cisplatin: Nephrotoxicity, Ototoxicity

XIX. Resources

  1. NCCN Clinical Practice Guidelines: Testicular Cancer
    1. https://www.nccn.org/professionals/physician_gls/default.aspx

XX. References

  1. Walsh (1998) Campbell's Urology, Saunders, p. 2411-45
  2. Baird (2018) Am Fam Physician 97(4):261-8 [PubMed]
  3. Horwich (2006) Lancet 367: 754-65 [PubMed]
  4. Kinkade (1999) Am Fam Physician 59(9):2539-44 [PubMed]
  5. Shaw (2008) Am Fam Physician 77: 469-76 [PubMed]

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Related Studies

Ontology: Testicular Neoplasms (C0039590)

Definition (NCI) A benign or malignant neoplasm that affects the testis. Representative examples include fibroma, thecoma, benign Sertoli cell tumor, seminoma, embryonal carcinoma, sarcoma, leukemia, and lymphoma.
Definition (MSH) Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms.
Definition (CSP) new abnormal testicular tissue that grows by excessive cellular division and proliferation more rapidly than normal and continues to grow after the stimuli that initiated the new growth cease.
Concepts Neoplastic Process (T191)
MSH D013736
SnomedCT 236778008, 126900000
English Neoplasm, Testicular, Neoplasms, Testicular, Neoplasms, Testis, Testis Neoplasms, Neoplasm, Testis, Testis Neoplasm, testis neoplasm, Testicular tumor, Testicular tumour, NEOPL TESTICULAR, TESTICULAR NEOPL, TESTIS NEOPL, NEOPL TESTIS, neoplasm of testis, neoplasm of testis (diagnosis), Testicular Neoplasms, Testicular neoplasm NOS, Testicular Neoplasms [Disease/Finding], testis tumor, testis tumors, testicular tumors, testicular tumour, testicular tumours, neoplasms testicular, tumor testicular, testicular tumor, testicular neoplasms, tumor testis, testicular neoplasm, Testicular Tumors, Testicular tumor (disorder), Testicular neoplasm, Tumor of testis, Tumour of testis, Neoplasm of testis (disorder), Neoplasm of testis, Testicular Neoplasm, Neoplasm of Testis, Neoplasm of the Testis, Testicular Tumor, Tumor of Testis, Tumor of the Testis
Italian Tumore del testicolo, Tumore del testicolo NAS, Neoplasie testicolari, Neoplasie del testicolo
Dutch testisneoplasma NAO, testisneoplasma, Gezwel, testis-, Gezwellen, testis-, Testisgezwel, Testisgezwellen
French Tumeur testiculaire SAI, Tumeur testiculaire, Tumeurs du testicule, Tumeurs testiculaires, Tumeurs des testicules
German Neubildung der Hoden NNB, Testikuläre Neoplasien, Neubildung des Hodens, Hodentumoren
Portuguese Neoplasia do testículo NE, Câncer de Testículos, Câncer do Testículo, Neoplasia do testículo, Neoplasias Testiculares
Spanish Neoplasia testicular NEOM, tumor testicular, tumor testicular (trastorno), Cáncer de Testículos, neoplasia de testículo (trastorno), neoplasia de testículo, Neoplasia testicular, Neoplasias Testiculares
Swedish Testikeltumörer
Japanese 精巣新生物ＮＯＳ, ｾｲｿｳｼﾝｾｲﾌﾞﾂ, ｾｲｿｳｼﾝｾｲﾌﾞﾂNOS, 睾丸新生物, 精巣新生物, 睾丸腫瘍, 精巣腫瘍
Finnish Kivesten kasvaimet
Russian IAICHKA RAK, TESTIKULIARNYI RAK, IAICHKA NOVOOBRAZOVANIIA, RAK IAICHKA, РАК ЯИЧКА, ТЕСТИКУЛЯРНЫЙ РАК, ЯИЧКА НОВООБРАЗОВАНИЯ, ЯИЧКА РАК
Czech Novotvar varlete NOS, Novotvar varlete, testikulární nádory, nádor varlete, nádory varlete, nádory varlat, testis - nádory
Croatian TESTIS, TUMORI
Polish Nowotwory jąder
Hungarian Testicularis neoplasia, Testicularis neoplasia k.m.n.
Norwegian Testikkelsvulster, Testikkeltumorer, Testikkelneoplasmer
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Malignant neoplasm of testis (C0153594)

Definition (MEDLINEPLUS)

Testicles, or testes, make male hormones and sperm. They are two egg-shaped organs inside the scrotum, the loose sac of skin behind the penis. You can get cancer in one or both testicles.

Testicular cancer mainly affects young men between the ages of 20 and 39. It is also more common in men who

  • Have had abnormal testicle development
  • Have had an undescended testicle
  • Have a family history of the cancer

Symptoms include pain, swelling, or lumps in your testicles or groin area. Doctors use a physical exam, lab tests, imaging tests, and a biopsy to diagnose testicular cancer. Most cases can be treated, especially if found early. Treatment options include surgery, radiation, and/or chemotherapy. Regular exams after treatment are important.

Treatments may also cause infertility. If you may want children later on, you should consider sperm banking before treatment.

NIH: National Cancer Institute
Definition (NCI) A primary or metastatic malignant neoplasm that affects the testis. Representative examples include seminoma, embryonal carcinoma, sarcoma, leukemia, and lymphoma.
Concepts Neoplastic Process (T191)
MSH D013736
ICD9 186
ICD10 C62 , C62.9, C62.90
SnomedCT 94087009, 188228003, 269472003, 363449006
English TESTIS NEOPLASM MALIGNANT, Malig neop testis NOS, Testicular cancer, Malignant neoplasm of testis, unspecified, Testis, unspecified, testicular cancer (diagnosis), malignant neoplasm of testis (diagnosis), malignant neoplasm of testis, testicular cancer, Testis neoplasm malignant, Cancer of the Testis, Cancers, Testis, Testis Cancer, Testis Cancers, Cancer, Testicular, Cancers, Testicular, Testicular Cancer, Testicular Cancers, malignant tumor of testis, Cancer of testis, Cancer of the Testes, cancer testicles, cancer testicular, cancer testicle, cancer testis, testicular cancers, Malignant neoplasm of testis NOS, Malignant neoplasm of testis, unspecified whether descended or undescended, Cancer, Testis, Malignant neoplasm of testis NOS (disorder), Testis cancer, Testis--Cancer, Testicular neoplasms malignant, Malignant tumor of testis, Malignant tumour of testis, Malignant tumor of testis (disorder), cancer of the testis, testicle cancer, testis cancer, Malignant neoplasm of testis, Malignant Neoplasm of Testis, Malignant Neoplasm of the Testis, Malignant Testicular Neoplasm, Malignant Testicular Tumor, Malignant Tumor of Testis, Malignant Tumor of the Testis, Cancer of Testis, Malignant neoplasm of testis, NOS, Neoplasm malig;testis, malignant neosplasm of the testis
Italian Cancro del testicolo, Tumori maligni del testicolo, Tumore maligno del testicolo, Tumore testicolare maligno, Cancro testicolare, Cancro dei testicoli
Dutch testiculaire kanker, maligne neoplasma van de testis, testisneoplasma maligne, Maligne neoplasma van testis, niet gespecificeerd, testikelneoplasmata maligne, testiskanker, Maligne neoplasma van testis, Testiskanker, Tumor van de testis
French Tumeur maligne d'un testicule, Tumeur testiculaire maligne, Cancer du testicule, TUMEUR MALIGNE DU TESTICULE, Tumeurs malignes testiculaires, Cancer testiculaire, Tumeur maligne du testicule, Tumeur maligne testiculaire
German Hodenneubildung boesartig, Hodentumor, boesartige Neubildung des Hodens, Krebs des Hodens, Boesartige Neubildung des Hodens, Boesartige Neubildung: Hoden, nicht naeher bezeichnet, HODEN NEUBILDUNG BOESARTIG, Neubildungen der Hoden boesartig, Hodenkrebs, Testikulärer Krebs
Portuguese Neoplasia maligna do testículo, Cancro do testículo, TUMOR MALIGNO DO TESTICULO, Câncer de Testículo, Câncer dos Testículos, Cancro testicular, Neoplasias malignas testiculares, Câncer Testicular
Spanish Neoplasia maligna de testículo, neoplasia testicular in situ, neoplasia maligna de testículo (trastorno), Cáncer de Testículo, NEOPLASIA TESTICULAR MALIGNA, neoplasia maligna de testículo, Cáncer de los Testículos, neoplasia maligna de testículo, SAI (trastorno), neoplasia maligna de testículo, SAI, tumor maligno de testículo (trastorno), tumor maligno de testículo, Neoplasias testiculares malignas, Cáncer testicular, neoplaisa testicular in situ, Cáncer Testicular
Japanese 精巣癌, 悪性精巣新生物, 精巣の悪性新生物, ｾｲｿｳﾉｱｸｾｲｼﾝｾｲﾌﾞﾂ, ｱｸｾｲｾｲｿｳｼﾝｾｲﾌﾞﾂ, ｾｲｿｳｶﾞﾝ
Czech Maligní novotvar varlete, Maligní nádor varlete, Maligní nádorové onemocnění varlete, Novotvary varlete maligní, Novotvar varlete maligní, testis - rakovina, testikulární rakovina, rakovina varlat
Korean 고환의 악성신생물, 상세불명 고환의 악성신생물
Hungarian Here rák, Here malignus daganata, Testicularis neoplasmák, rosszindulatú, Rosszindulatú hereneoplasia, Hererák
Norwegian Testikkelkreft, Cancer testis
Derived from the NIH UMLS (Unified Medical Language System)

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